The mammalian fetus and neonate are known to be susceptible to the effects of chemical carcinogens. We are attempting to develop animal models for evaluation of the oncogenic risk carried by the humans fetus and newborn. In continuation of ongoing work the following projects are proposed: 1. Role of fetal or newborn metabolic activation/detoxification of chemical carcinogens through mixed-function oxygenase (MFO) activity in determining tumorigenicity. Transplacental induction of MFO activity in the fetus or newborn will be followed by carcinogen treatment. Tumor incidence in the offspring is to be compared with that in control offspring (inducer only, carcinogen only, and no treatment groups). 2. Effect of chronic low-dose exposure to environmental carcinogens. Our preliminary results suggest that dimethylnitrosamine (DMN) may have a tumorigenic effect even at known environmental levels (10 ppb) if administered throughout the life cycle. Strain A mice with high sensitivity to lung adenosine induction will be adminstered 10 ppb DMN in their drinking water from preconception until sacrificed at 6 months of age and their lung tumors counted. 3. N6(methylnitroso) adenosine, formed by interaction of nitrite with a naturally occurring RNA riboside, has been recently demonstrated by us to be a potent tumorigen in the newborn mouse and a weak transplacental tumorigen. Possible pathways of metabolic activation of this carcinogen will be investigated.